Monitoring mechanical heart properties

ABSTRACT

In a method and system for monitoring mechanical properties of a heart in a subject, multiple cardiogenic impedance values reflective of the impedance of the heart in connection with a transition from inhalation to exhalation in the subject are determined. Correspondingly, multiple cardiogenic impedance values reflective of the impedance of the heart in connection with a transition from exhalation to inhalation are determined. The impedance values are collectively processed to form a trend parameter. The value determination and processing is performed over several respiratory cycles spaced apart in time to form a plurality of trend parameters over time. The mechanical properties of the heart are monitored by processing these different trend parameters. The data collection and optionally at least a part of the data processing is performed by an implantable medical device.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention generally relates to heart monitoring, and inparticular to methods and devices for monitoring the mechanicalproperties of the heart.

2. Description of the Prior Art

The heart is an essential organ in humans and most animals, pumpingblood throughout the human/animal body. As a consequence, it isfundamentally important that the mechanical pumping properties of theheart operate correctly.

There are several diseases and conditions that negatively affect thesemechanical properties of the heart, including cardiac ischemia. Cardiacischemia is a condition where the flow of oxygen-rich blood to the heartmuscle is restricted. This form of ischemia occurs when an arterybecomes narrowed or blocked for a short time, preventing oxygen-richblood from reaching the heart. If ischemia is severe or lasts too long,it can cause a heart attack (myocardial infarction) and can lead toheart tissue death. In most cases, a temporary blood shortage to theheart causes pain of angina pectoris. This will then be an indication tothe patient that something is not right and he/she should contact aphysician.

However, in other cases, there is no pain. These cases are called silentischemia in the art. This is a severe condition as the patient may notnotice that an ischemic condition has occurred or is present and willtherefore not contact a physician.

The American Heart Association estimates that 3 to 4 million Americanshave episodes of silent ischemia. People who have had previous heartattacks or those who have diabetes are especially at risk for developingsilent ischemia. Heart muscle disease (cardiomyopathy) caused by silentischemia is among the more common causes of heart failure in the UnitedStates.

Today there are two main tests that can be used to diagnose silentischemia. Firstly, an exercise stress test can show blood flow throughthe coronary arteries in response to exercise, usually walking on atreadmill. Secondly, Holter monitoring records the heart rate and rhythmover at least a 24-hour period. The patient wears a recording device,the Holter monitor, which is connected to disks on the chest. Aphysician can then look at the printout of the recording to find out ifthe patient has had episodes of silent ischemia while he/she was wearingthe Holter monitor.

However, these two tests require the active participation of aphysician. The Holter monitoring is further limited as episodes ofsilent ischemia must occur during the actual monitoring and previousepisodes of ischemia may remain unnoticed. In addition, it is highlyunlikely that a patient suffering from attacks of silent ischemia indeedwill contact a physician and undergo one of the prior art tests. Assilent ischemia seldom has any symptoms, the patient is not aware of thedeleterious condition and will therefore not visit a physician.

There are also other conditions and diseases that affect the mechanicalproperties of the heart in addition to ischemia. For example, heartinfarcts cause necrosis of the heart tissue, poor inter-chambersynchronization will cause remodulation while other heart failures canlead to increased heart size (hypertrophy).

The document EP 1 384 433 discloses an apparatus for early detection ofan ischemic heart disease. The apparatus comprises means for measuringan intracardiac impedance of a patient's heart and generating acorresponding impedance signal. A notch detector is provided fordetecting the occurrence of a notch in the impedance signal coincidentwith the entry of blood into the ventricle. The apparatus also comprisesa pattern recognition means for comparing the measured post-notchimpedance curve with a stored predetermined reference impedance curvetemplate to detect an ischemic heart disease.

There is therefore a need for a monitoring of the mechanical propertiesof the heart that can be used for detecting ischemia or another heartdisease or condition affecting these properties. In particular, suchmonitoring should be able to also detect of silent ischemia and otherunnoticed heart failures.

SUMMARY OF THE INVENTION

The present invention overcomes these and other drawbacks of the priorart arrangements.

It is a general object of the present invention to provide a monitoringof mechanical properties of the heart of a subject.

It is a particular object of the invention to provide a heart propertymonitoring that could be used in connection with heart diagnosing.

It is another particular object of the invention to provide a heartproperty monitoring useful in detecting silent ischemia and otherunnoticed heart failures.

These and other objects are met by the invention as defined by theaccompanying patent claims.

Briefly, the present invention involves methods, devices and systems formonitoring mechanical properties of a heart in a subject, preferablymammalian subject and more preferably a human subject.

The monitoring involves determining a first set of multiple cardiogenicimpedance values of the subject. These impedance values are reflectiveof the impedance of the subject's heart in connection with a transitionfrom inhalation to exhalation in the subject. In other words, theseimpedance values reflect the cardiogenic impedance at or near maximumlung volume or inflation. Correspondingly, a second set of multiplecardiogenic impedance values are also determined. These values arereflective of the impedance of the heart in connection with a transitionfrom exhalation to inhalation in the subject. The values are, thus,reflective of the cardiogenic impedance at or near minimum lung volume.

The impedance values in these two sets are collectively processed toform or generate a trend parameter. This trend parameter will be anindication or estimate of the difference in cardiogenic impedance atdifferent occasions in the respiratory cycle. The determination of thecardiogenic values in connection with subject exhalation and inhalationare performed during several such exhalation-inhalation andinhalation-exhalation transitions. Each such set pair (first and secondset) is then collectively processed to form trend parameters. The resultof these multiple data processings is thus a plurality of trendparameters over times.

The mechanical properties of the subject's heart are monitored byprocessing the plurality of trend parameters. This processing may, forexample, include plotting the trend parameters in a diagram versus timeto allow detection of any sudden change in the parameter values, whichmay be an indication of a deleterious change in the mechanicalproperties of the subject's heart.

In a preferred implementation, impedance measurements are used not onlyfor determining the cardiogenic impedance values employed for generatingthe trend parameters. Impedance values representative of the respiratoryimpedance of the subject can be used for identifying when thetransitions between inhalation/exhalation and exhalation/inhalationoccur. This means that this respiratory impedance is useful foridentifying when cardiogenic impedance measurements should be performedor for identifying those cardiogenic impedance values that coincidencewith or fall close to a respiration transitions.

The measurement of the cardiogenic and the preferred respiratoryimpedance used in the monitoring of the present invention is preferablyperformed by an implantable medical device, e.g. pacemaker, cardiacdefibrillator or cardioverter, implanted in the subject.Correspondingly, at least a portion of the data processing conducted inthe monitoring of the invention may be implemented in the implantablemedical device. Alternatively, or in addition, the data processing isperformed by an external device in wireless communication with theimplantable medical device based on raw data or partly processed datafrom the implanted device. In such a case, this external device cantrigger an alarm notifying the subject or a physician if the mechanicalproperty monitoring of the invention detects any deleterious heartcondition.

The invention offers the following advantages:

Can be used in connection with early detection of deleterious heartconditions affecting the mechanical heart properties;

Allows detection of silent and symptom-free conditions such silentischemia; and

Can be implemented using traditionally employed impedance-measuringequipment.

Other advantages offered by the present invention will be appreciatedupon reading of the below description of the embodiments of theinvention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a flow diagram illustrating a method of monitoring mechanicalheart properties according to the present invention.

FIG. 2 is a flow diagram illustrating an embodiment of the determiningsteps of FIG. 1 in more detail.

FIG. 3 is a flow diagram illustrating another embodiment of thedetermining steps of FIG. 1 in more detail.

FIG. 4 is a flow diagram illustrating an embodiment of the detectingsteps of FIG. 2 or FIG. 3 in more detail.

FIG. 5 is a diagram illustrating results of cardiogenic impedancemeasurements according to the present invention.

FIG. 6 is a diagram illustrating results of respiratory impedancemeasurements according to the present invention.

FIG. 7 is a diagram illustrating fitting an ellipse to cardiogenicimpedance values according to the present invention.

FIG. 8 is a diagram illustrating fitting a straight line to cardiogenicimpedance values according to the present invention.

FIG. 9 is a diagram illustrating cardiogenic impedance values collectedaccording to the present invention.

FIG. 10 illustrates diagrams of different trend parameters useful inmonitoring mechanical heart properties of the present invention.

FIG. 11 illustrates diagrams of the trend parameters in FIG. 10 beforeand after an induced chronic hear failure.

FIG. 12 illustrates diagrams displaying cardiogenic impedance valuesbefore (left) and after (right) induced heart ischemia.

FIG. 13 is a diagram illustrating multiple loops of FIG. 12 before andafter induced heart ischemia.

FIG. 14 is a diagram illustrating monitoring of a trend parameterdetermined from the diagram of FIG. 13.

FIG. 15 is a diagram illustrating monitoring of another trend parameterdetermined from the diagram of FIG. 13.

FIG. 16 schematically illustrates a patient equipped with an implantablemedical device according to the invention and the communication betweenthe implantable medical device and an external programmer.

FIG. 17 is a schematic block diagram of a monitoring system according tothe present invention.

FIG. 18 is a schematic block diagram illustrating an embodiment of thedata processor of FIG. 17 in more detail.

FIG. 19 is a schematic block diagram of an implantable medical deviceaccording to the present invention.

FIG. 20 is a schematic block diagram illustrating an embodiment of theimpedance calculator of FIG. 19 in more detail.

FIG. 21 is a schematic block diagram of an implantable medical deviceaccording to the present invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

Throughout the drawings, the same reference characters will be used forcorresponding or similar elements.

The present invention generally relates to methods, devices and systemsfor monitoring the mechanical properties of the heart in a subject,preferably a mammalian subject and more preferably a human subject.These mechanical properties include the function of the heart in pumpingblood through the pulmonary circuit/system and the systemiccircuit/system.

By monitoring the mechanical heart properties it is possible to detect,even at an early instant, a change in the properties caused by differentconditions directly effecting or indirectly effecting the subject'sheart. For example, cardiac ischemia and other ischemic heart diseases,including heart infarcts, will cause stiffness to at least a portion ofthe heart muscle. This in turn affects the pumping function and therebythe mechanical properties of the heart. Other deleterious conditionsaffecting these mechanical properties include other forms of heartfailure leading to increased heart size (hypertrophy) and poorinter-chamber synchronization causing tissue remodulation.

The monitoring of the present invention is based on measurement andprocessing of the cardiogenic impedance. As is used herein, cardiogenicimpedance refers to impedance signals originating from the heart. Thecardiogenic impedance is an impedance signal, preferably recorded insidethe body of a subject, filtered to enhance the frequencies originatingfrom the heart's mechanical activity.

Impedance recorded inside the body will consist of several differentparts. There is one part originating from the (rather) constant amountof tissue between and in the vicinity of the electrodes used formeasuring the impedance. This is a very slowly shifting part of thesignal and is affected by, among others, the body composition. The lungstake up a large part of the thorax and each respiratory cycle affectsthe impedance as well. This is in part due to the fact that theincreased amount of air in the thorax decreases conductivity, but alsobecause of mechanical effects, e.g. tilting other organs, fat deposits,etc. altering what the measured impedance “sees”. There is also a fastershifting part originating from the activity of the heart. If theimpedance vector is inside or across the heart, the signal is composedin part of the shifting amount of blood the impedance vector sees and inpart due to mechanical deformation. This does not necessary require thatthe actual heart is spanned by the impedance vector. In fact, the samekind of variations is obtained if the impedance is measured in the leg.

It has been discovered that the morphology of hear, as determined by thecardiogenic impedance, changes depending upon where a heart beat isoccurring in the respiratory cycle. This respiratory cycle comprises auser inhalation and the following user exhalation or a user exhalationand the following inhalation, depending on where the start point of therespiratory cycle is defined. These morphological differences are notsimple amplitude differences but have other fundamental origins. Withoutbeing bound by theory, a very fast regulatory system may be present thatadapts the contraction pattern or stroke volume of the heart dependingon the breathing, as signaled by, for example, oxygen saturation (SO₂)in the blood of the pulmonary vein. This regulatory system would thenoperate on a beat-to-beat basis. Alternatively, or in addition, thelungs mechanically influence the heart. Thus, during inhalation the lungvolume increases and the lungs take up more space in the thorax,slightly altering the heart's geometry, e.g. by tilting and compressingthe heart slightly. It is proposed that both theserespiratory-originating effects will be a cause of the morphologicaldifferences.

These inter-beat variations in the cardiogenic impedance significantlychange with a change in the mechanical properties of the heart. Thus,the difference in cardiogenic impedance in connection with maximum lungvolume (filled lungs) and minimum lung volume (empty lungs) will changeas the mechanical properties or the heart change, as illustrated byexposing the heart to certain provocations or a deleterious heartcondition.

In the prior art, the respiratory dependence of the cardiogenic signalis most often, more or less effectively, filtered away. In clearcontrast, the present invention acknowledges it and uses the informationhidden in the respiratory effect on the cardiogenic impedance.

FIG. 1 is a flow diagram illustrating a method of monitoring mechanicalproperties of a heart in a subject according to an embodiment of thepresent invention. The method starts in step S1, where a first set ofmultiple cardiogenic impedance values are determined. These impedancevalues are reflective of the impedance of the heart in connection with atransition from inhalation to exhalation in the subject. Thus, theseimpedance values reflect the cardiogenic impedance at or close tomaximum lung volume. A next step S2 determines a corresponding secondset of multiple cardiogenic impedance values. These values arereflective of the cardiogenic impedance in connection with a transitionfrom exhalation to inhalation in the subject. This means that the valuesreflect the cardiac impedance at or close to minimum lung volume.

The impedance values of the first and second set are collectivelyprocessed in a next step S3. This collectively processing involvesdetermining or estimating a trend parameter based on the cardiogenicimpedance values determined in steps S1 and S2. This trend parameter isindicative of the morphological difference in the cardiogenic impedancesignal in connection with inhalation-exhalation transition as comparedto exhalation-inhalation transition.

The determining steps S1 and S2 and the collectively processing step S3is repeated multiple times as schematically illustrated by the line L1.This means that a plurality of trend parameters will be determined,where each such trend parameter is generated from the cardiogenicimpedance values of a respective pair of first and second value sets. Asthese trend parameters reflect the morphological cardiogenic impedancedifference over time, they are used in a next step S4 to monitor themechanical properties of the heart. Thus, the trend parameters obtainedby repeating the loop of steps S1 to S3, or at least a portion thereof,are processed in step S4 for proving this property monitoring.

It is possible to use different time frames when repeating the loop ofsteps S1 to S3. For example, these steps S1 to S3 could be conductedseveral times during a day and night, such as every few hours. Changesin the mechanical properties occurring during that day can then be earlydetected. However, for most practical implementation it might be enoughto collect trend parameters once per day, every second day, every thirdor even more seldom.

In further embodiment, multiple trend parameters can be generated perday and the average of these parameters are calculated and stored forusage in the monitoring. In such a case, only one trend parameter needto be stored per measuring day, but this value will be an average ofmultiple values collected during different time instances that day. Thiswill level out any background noise due to different subject postures,physical activity and other factors that could have an effect on themeasurements. The monitoring of step S4 will then be conducted based ofmultiple average trend parameters, each being averaged over one day, apart of a day or a longer period than a day.

In the case of a change in the mechanical properties of the heart, suchas an ischemic condition, this change will be reflected in the values ofthe trend parameters. This means that the processed trend parameters canbe employed as decision support information for deciding whether adeleterious heart condition is present and whether any actions should betaken.

The method then ends.

FIG. 2 is a flow diagram illustrating an embodiment of the determiningsteps S1 and S2 of FIG. 1 in more detail. The method starts in step S10,where it is identified whether the subject has inhaled and is about tostart exhaling, i.e. whether the subject is in the transition frominhalation to exhalation in the respiratory cycle. In such a case themethod continues to step S12 where a current signal or a voltage signalis applied to subject. In a preferred embodiment, this current/voltagesignal is applied using electrodes implanted in the thorax of thepatient, such intra-thoracic, intra-cardiac and/or epi-cardiacelectrodes. The usage and positioning of such implanted electrodes willbe described in further details herein.

The applied current and voltage signal is preferably in the form of atrain of current or voltage pulses. In the art of impedance measurement,different such pulse trains have been suggested. Any such prior artknown pulse-based signal can be used in connection with the presentinvention. Thus there is a freedom in selecting particular pulse shape(amplitude(s), pulse form, current/voltage step or change, duration,etc.). In addition, the sampling rate, i.e. the time between applyingthese current or voltage pulses can also non-inventively be selected bythe person skilled in the art. In order to provide a suitable amount ofresulting voltage or current values a sampling rate of at least about 10Hz is preferred, preferably at least about 50 Hz. An example of acurrent pulse tested with good result first applies a negative currentpulse, directly followed by a positive current pulse and then ends witha second negative current pulse. The two negative current pulsespreferably have same amplitude and duration. Examples of suitablecurrent amplitudes include −250 μA, −187.5 μA, −125 μA and −62.5 μA. Thepositive pulse could, for example, have any of the following amplitudes1000 μA, 750 μA, 500 μA, 250 μA. The current pulse width could be in theinterval of 14 μs to 40 μs.

Possible sampling rates that could be used include, but are not limitedto, 16 Hz, 32 Hz, 64 Hz and 128 Hz.

In a next step S13, a resulting voltage or current signal is measuredusing a pair of electrodes, preferably implanted electrodes in thesubject. If a current signal, such as current pulse, was applied in stepS12, the step S13 measures a resulting voltage signal and vice versa.The same electrodes used for applying the current/voltage signal can beused for measuring the resulting voltage/current signal, i.e. a bipolarelectrode arrangement is employed. Alternatively, one of the electrodescould be common for the signal application and the signal measurement,i.e. a tripolar arrangement, or dedicated application and measurementelectrodes could be employed, denoted quadropolar arrangement in theart.

Information of the applied current/voltage signal and the measuredvoltage/current signal is used in step S14 for calculating thecardiogenic impedance in connection with the inhalation-to-exhalationtransition. The “area” of the current (voltage) pulse is known and the“area” of the sensed voltage (current) is computed. A cardiogenicimpedance value is then calculated as the ratio between the voltage andthe current.

As the applied signal is preferably in the form of multiple separatecurrent or voltage pulses, multiple cardiogenic impedance values can becalculated in step S14 and constitute the first value set of theinvention.

In a preferred implementation of the invention, the application of thecurrent or voltage signal in step S12 is preferably performed during aheart cycle or cardiac cycle occurring in connection with theinhalation-to-exhalation transition. As is well-known in the art, acardiac cycle involves the three major stages: atrial systole,ventricular systole and cardiac diastole. A cardiac cycle can, forinstance, be defined as the period from one R-wave to the next, i.e. asso-called RR-interval. This should, however, merely be seen as anillustrative and non-limiting example of defining the start point andend point of a cardiac cycle.

In a more preferred implementation, the current or voltage signal isapplied in step S12 in connection with a defined period of the cardiaccycle coincident with or being close, preferably closest, in time to theinhalation-to-exhalation transition. This defined period is preferablythe period of the cardiac cycle where the cardiogenic impedance islargest, i.e. corresponds to peak in the impedance. This periodgenerally corresponds to the interval from about 100 ms to about 400 msfollowing an R-wave. However, the actual position of the intervalfollowing an R-wave may differ slightly depending on subject age, sex,health condition, activity level, etc.

The method then continues to step S10 for also generating multiplecardiogenic impedance values for the second value set, which isschematically illustrated by the line L2.

If it is determined that the current state in the respiratory cycle isnot an inhalation-to-exhalation transition the method continues fromstep S10 to step S11. In this step S11, it is identified whether therespiratory state is in the transition from exhalation to inhalation. Ifthis is not the case, the method continues anew to step S10.

However, if the state is an exhalation-to-inhalation transition, themethod continues to step S12, where a current or voltage signal isapplied. The operation of this step S12 and the following steps S13 andS14 is conducted in the same manner as previously described. Thecardiogenic impedance values calculated in step S14 are thus reflectiveof the cardiogenic impedance during the exhalation-to-inhalationtransition, preferably during a cardiac cycle occurring in connectionwith (coincident with or being close to) the transition and morepreferably during the defined period of that cardiac cycle. Theresulting cardiogenic impedance values constitute the second value setof the invention.

The method then continues to step S3 of FIG. 1 where the calculatedimpedance values of the first and second sets are collectively processedto generate a trend parameter.

It is anticipated by the present invention that the order of steps S10and S11 can be interchanged without affecting the result of theoperation of the invention.

FIG. 3 is a flow diagram illustrating another embodiment of thedetermining steps S1 and S2 of FIG. 1 in more detail. The method startsin step S20, where a current or voltage signal is applied to thesubject. This step basically corresponds to step S12 of FIG. 2 and isnot described further herein. The resulting voltage or current signalsare measured in a next step S21, which is performed as previouslydescribed in connection with step S13 of FIG. 2.

In an optional step S22, information of the applied signal and themeasured signal is employed for calculating cardiogenic impedancevalues. This is performed as described in connection with step S14 ofFIG. 2. Thereafter it is determined whether the respiratory cycle stateis in the transition from inhalation to exhalation in step S23 or in thetransition from exhalation to inhalation in step S24. If respiratorystate is neither of these transitions the method is returned to stepS20, which is schematically illustrated by the line L3.

If, however, the state is one of the transitions, the method continuesto step S25, where cardiogenic impedance values are calculated unlessthis was performed in step S22. The operations in this step S25 aresimilar to those in step S14 of FIG. 2. In either case, the cardiogenicimpedance values occurring in connection with theinhalation-to-exhalation transition or the exhalation-to-inhalationtransition, preferably occurring during a cardiac cycle occurring inconnection with the transition and more preferably during the definedperiod of that cardiac cycle, are tagged in step S26. This value taggingidentifies whether the cardiogenic impedance values belong to the firstvalue set or the second value set of the invention.

Once cardiogenic values of both the first set and the second set havebeen calculated and tagged, the method continues to step S3 of FIG. 1,where a trend parameter is calculated from the values.

In contrast to FIG. 2, this embodiment involves continuously orperiodically applying a current or voltage signal and measuring theresulting voltage or current signal during a measuring period. Thismeans that several of the measured voltage/current values and calculatedimpedance values if step S22 is performed will not be used according tothe invention. Only those voltage/current values and calculatedimpedance values measured in connection with theinhalation-to-exhalation and exhalation-to-inhalation transitions, morepreferably such values registered through a cardiac cycle, or a definedportion of a cardiac cycle occurring in connection with the transitions,will be employed for the purpose of the invention.

Different techniques can be employed for determining where in therespiratory cycle, the cardiogenic impedance values should be collectedto coincidence with or falling close to the transitions betweeninhalation and exhalation and vice versa. For example, external stretchsensors and gauges or pressure sensors could be connected to the chestof the patient for following the movement of the lungs. In a similarmanner, implanted stretch or pressure sensors could alternatively beused for synchronizing the cardiogenic impedance measurement or taggingwith the correct intervals (transitions) in the respiratory cycle. Afurther possible technique could be the recording of intra-cardiacelectrograms (IEGMs). The respiratory signal can be identified bylow-pass filtering the IEGM signal, e.g. by using a cut-off frequency ofabout 0.2-0.5 Hz. Still another possibility is to use the measuringtechnique described above in connection with FIG. 3, in other words,more or less continuously or periodically measure the cardiogenicimpedance during measurement intervals. A copy of this impedance signalcan then be low-pass filtered in similarity to the IEGM signal (cut-offfrequency of about 0.2-0.5 Hz) to follow the respiratory signal.

FIG. 4 is a flow diagram illustrating a further possibility ofidentifying the inhalation-to-exhalation and exhalation-to-inhalationtransitions in the respiratory cycle. The method continues from start inFIG. 2 or step S22 in FIG. 3. In a next step S30, a respiratoryimpedance signal comprising multiple respiratory impedance values isgenerated. This respiratory or respiration impedance can be used as anindication of or for following respiratory volume changes. Therespiratory impedance is accomplished by the passing of a very smallelectrical current (or voltage) across the subject's chest electrodesand measuring the change in impedance as the chest volume changes. Theimpedance is a result of air (which is a poor electrical conductor),moving into the lungs and thereby changing the volume of the lungs. Itis often possible to obtain this respiratory impedance signal from thesame applied current/voltage signal and the resulting measuredvoltage/current signal as was used for generating the cardiogenicimpedance signal. This possible by applying different filtering to theraw impedance signal to get both the cardiogenic impedance signal andthe respiratory impedance signal. In a preferred implementation, therespiratory impedance of the invention is respiratory AC impedance.

FIG. 6 is a diagram of the respiratory signal from a bipolar recordingfrom the ring electrode of a right ventricular (RV) lead to the can. Therespiratory cycle is clearly evident from such a recording. Therespiratory impedance increases during inhalation up to the peak (localmaximum) corresponding to the transition from inhalation to exhalation.At this peak, the volume of the lungs is at maximum during the cycle. Asthe subject exhales the respiratory impedance drops down to a localminimum or minimum plateau. At this minimum the transition fromexhalation to inhalation is taking place. This corresponds to minimumlung volume during the cycle.

In FIG. 4, the recorded respiratory impedance signal is monitored instep S30 to identify, in step S31, the transitions taking place in therespiratory cycle. In other words, this identifying step S31 identifiesthe maximum and minimum points or plateaus in the respiratory cycle. Thecardiogenic impedance values of the invention are then collected ortagged in connection with the maximum and minimum values/plateaus instep S12 of FIG. 2 or step S25 of FIG. 3.

In a typical implementation, the cardiogenic cycles coinciding with orbeing closest in time to the maximum or minimum value of the respiratoryimpedance during a respiratory signal are identified. The cardiogenicimpedance values are then generated or tagged during these identifiedcardiogenic cycles or more preferably during defined periods of theidentified cycles.

It is anticipated by the present invention that for most practicalimplementation it is not absolutely necessary to employ cardiogenicimpedance values occurring during the heart cycle being closest in timeto the peaks and valleys in the respiratory impedance signal. Forexample, a first cardiogenic cycle might occur shortly before a peak inthe respiratory signal with a second cardiogenic cycle occurring shortlyafter the peak. This second cycle could be closer in time to the peaktop as compared to the first cycle. However, the monitoring of themechanical properties of the invention may indeed be successfullyperformed even when employing the first cardiogenic cycle over thesecond cycle. Thus, it is necessary that the cardiogenic impedancevalues of the invention are collected in connection with the respiratorytransitions (maximums and minimums) but they must not necessarilycoincident with the transitions. It may actually more advantageous forsome heart conditions to select cardiogenic cycles not being closest intime to the peaks and values, such as the first cycle above. Forexample, the cardiogenic impedance values recorded during at least aportion of the cardiogenic cycle occurring closest to themaximum/minimum values in FIG. 6 but on a defined position relative themaximum/minimum values. Thus, impedance values collected close to theend of the inhalation stage (or at the beginning of the exhalationstage) of the respiratory cycle could be used as impedance valuesoccurring in connection to the inhalation-to-exhalation transition.Correspondingly, impedance values collected close to the end of theexhalation stage (or at the beginning of the inhalation stage) are usedas such values occurring in connection with the exhalation-to-inhalationtransition.

Depending on how the subject is actually inhaling and exhaling, thepeaks and/or valleys in FIG. 6 could instead be maximum or minimumplateaus. In such a case, it could be possible that at least twocardiogenic cycles take place during such a plateau in the respiratorysignal. The cardiogenic impedance values recording at a period of any ofthese at least two cardiogenic cycles could then be employed accordingto the invention.

FIG. 5 is a diagram illustrating the cardiogenic impedance signalrecorded as taught by FIG. 3, i.e. more or less continuously during atime interval. In this case, bipolar measurements between RV ringelectrode and can electrode have been used to generate the cardiogenicimpedance signal. In the upper plot, the respiratory cycles are evident,slowly modulating the signal. The lower plot is a magnification of theimpedance signal during the respiratory cycle marked in the upper plot.In this plot it is clearly shown that the cardiogenic content of theimpedance signal changes depending on where we are in the respiratorycycle.

As was described in the foregoing, the cardiogenic impedance values arepreferably determined for a defined period of a cardiac cycle, where thedefined period corresponds to the peak of the impedance signal. In thelower plot several such cardiac cycles are illustrated. The definedperiod corresponds to the peak of the cardiogenic impedance. Forexample, if the cardiogenic cycle corresponding to sample 2725 to 2800coincidences with the exhalation-to-inhalation transition, the impedancevalues corresponding to sample 2737.5 to 2780 could be useful in themonitoring of the invention.

The collectively processing of the cardiogenic impedance values of thetwo value sets collected during a same respiratory cycle can beperformed in vastly different manners. In a preferred approach, theimpedance values of the second value set (or first value set) areregarded as functions of the impedance values of the first value set (orsecond value set). The impedance values could then be plotted with thesecond set values on the y-axis and the first set values on the x-axis.If the two sets do not contain the same number of impedance values,spline interpolation can be employed to form equally large sets. FIGS. 7and 8 are two diagrams illustrating such a value plotting. It is clearfrom these diagrams that the cardiogenic impedance is differentdepending on where it is measured in the respiratory cycle, otherwiseall plotted points would lie on a straight line with slope k=1.

The trend parameter is obtained by processing the plot points depictedas “*” in the diagrams. The trend parameter of the invention is aquantity reflecting the respiratory difference in the cardiogenicimpedance. Starting from the collected impedance values and generatingthe plot points as illustrated in FIGS. 7 and 8, different parametersreflecting the difference in the cardiogenic impedance values can bedetermined.

FIG. 7 illustrates a first possible approach. In this approach anellipse is fit to the plot points. This ellipse is preferable theellipse that fit best to the points in sense of minimizing the meansquare error (MSE) or some other error estimate. The trend parameter isthen a parameter representative of the fitted ellipse. For example, themajor axis of the ellipse illustrated in FIG. 7 can be used as a trendparameter of the invention. In addition, or alternatively, the anglebetween the major axis and the x-axis (also illustrated in FIG. 7) couldbe used as a trend parameter.

In a different approach, a straight line is fitted to the plot points asis shown in FIG. 8. This line is preferably the line that minimizes theMSE and can therefore be regarded as the straight line that best fits tothe points. The trend parameter is then a parameter representative ofthe straight line, such as the slope of the line. Another example is touse the mean value of the squared difference between an estimated plotvalue and a true plot value as trend parameter. Thus, for each impedancevalue, x, of the first set, the corresponding “true” impedance value ofthe second set, y_(T), and estimated value, y_(E), as determined fromthe straight line are identified. The trend parameter T is thencalculated as:

$T = \frac{\sum\limits_{i = 1}^{N}\left( {y_{T}^{i} - y_{E}^{i}} \right)^{2}}{N}$where N is the number of values of the first (and second) value set.Instead of using the mean squared error as trend parameter, thecorrelation coefficient is computed from the covariance matrix. Thiscorrelation coefficient is then employed as trend parameter.

A slightly different approach is illustrated in FIG. 9. The two diagramsillustrate the different impedance values registered in connection witha cardiogenic cycle occurring in connection withinhalation-to-exhalation transition and exhalation-to-inhalationtransition. In the figure, yy2 denotes the impedance values of thesecond set and yy1 denotes the values of the first set. The peak sectionof the two data sets, marked as a bold line in the figure, isidentified. For each such top section, the variance among the selectedsamples is computed, resulting in two variance numbers. The trendparameter can then be calculated from these two variance numbers, suchas the ratio between them.

The above given examples of calculated trend parameters should merely beseen as illustrative approaches of trend parameters that can be usedaccording to the invention. Actually any parameter that is descriptiveof the difference in cardiogenic impedance at the two measuringoccasions (transitions) of a respiratory cycle can be used as trendparameter of the invention.

The trend parameter could also be a combination of two or moreparameters. For instance, multiplying the ellipse major axis with theellipse angle (in radians), gives a number that can be used as trendparameter.

In the monitoring of the mechanical properties of the heart, multipletrend parameters calculated as previously described and representativeof different measuring periods are processed. In such a case, the trendparameters are preferably of a same type. Thus, they could all representellipse major axis or some other of the previously mentioned parametertypes. The trend parameters can then be plotted over time to display anychange in the mechanical properties of the heart.

FIG. 10 is a diagram illustrating different such trend parameters overtime. The diagrams are the result of ischemic experiments, whereischemia is induced in adult porcine through injection of micro spheres(sephadex provocation) in the left anterior descending coronary arteryon the left side of the heart. This causes blocking of the coronarycapillaries, causing a rather global ischemia. The onset of the microsphere provocation is almost immediate and the vertical lines denotemaximum provocation effect (with respect to change in contractility,cardiac output, stress, etc.). The following period corresponds to therecovery part. For the variance ratio, no impedance values were recordedduring the provocation but merely in the recovery part.

FIG. 11 illustrates diagrams from experiments on a chronic heart failure(CHF) model on canine. This heart failure is induced through rapidpacing for several weeks. In these experiments, no posture knowledge wasavailable as the animals were awake and free to move during the trails.In each diagram, two trend parameters from different times in healthyanimal (at x=1) and two trend parameters from the same animal afterheart failure was confirmed (x=2) are illustrated. From these diagramsit is clear that usage of ellipse major axis, ellipse angle orcorrelation parameter as trend parameter provides a good discriminationbetween healthy heart tissue and CHF.

FIG. 12 illustrates a loop of a cardiogenic impedance values during arespiratory cycle, where the values of the second value set have beenplotted as functions of the impedance values of the first set. Theleftmost plot corresponds to healthy heart tissue, whereas the rightmostplot is after sephadex provocation, i.e. after cardiogenic ischemia. Inclear contrast to the diagrams of FIGS. 7 and 8, the plot points are nowinterconnected to form the illustrated loops. FIG. 13 illustratesseveral overlaid loops of FIG. 12 over time. In this diagram, the lightgray loops are the results before provocation and the dark loops areafter provocation. It is clear from this figure that there is differencein impedance values before and after provocation as the loops afterischemia have markedly different shape as compared to the pre-ischemialoops.

FIGS. 14 and 15 are diagrams over trend parameters from impedance valuesrecorded before and during the onset of ischemic condition. In FIG. 14,the trend parameter is in the form of the slope of a line fitted to plotpoints (loop) and in FIG. 15, the correlation coefficient is used astrend parameter. There is a clear reduction in the slope followingischemia in FIG. 14, whereas the variance of the correlation increasesafter ischemia in FIG. 15.

The methods according to the present invention may be implemented assoftware, hardware, or a combination thereof. A computer program productimplementing the methods or a part thereof comprises software or acomputer program run on a general purpose or specially adapted computer,processor or microprocessor. The software includes computer program codeelements or software code portions that make the computer perform themethods using at least one of the steps previously described in FIGS. 1to 4. The program may be stored in whole or part, on, or in, one or moresuitable computer readable media or data storage means such as amagnetic disk, CD-ROM or DVD disk, USB memory, hard disk,magneto-optical memory storage means, in RAM or volatile memory, in ROMor flash memory, as firmware, or on a data server.

FIG. 16 is a schematic overview of a subject 1 equipped with animplantable medical device (IMD) 200 connected to the subject's heart10. The IMD 200 is illustrated as a device that monitors and/or providestherapy to the heart 10 of the patient 20, such as a pacemaker,defibrillator or cardioverter. However, the present invention is notlimited to cardiac-associated IMDs but may also be practiced with otherimplantable medical devices, such as drug pumps, neurologicalstimulators, physical signal recorders, oxygen sensors, or the like, aslong as the IMD 200 is equipped with or is connected with equipment 210allowing measurement of the cardiogenic impedance of the subject's 1heart 10.

In the figure, the IMD 200 is connected to two leads 210 inserted intothe heart 210 and the right and left ventricle. These leads 210 areequipped with electrodes, such as tip electrodes, ring electrodes and/orcoil electrodes, depending on what impedance vector is desired. The IMD200 must not necessarily have two different leads but could instead usea single lead. Depending on the number of leads 210 and theirintra-cardiac position, different impedance vectors are possible andwithin the scope of the invention. For example, the impedance vectorcould be between right ventricle (RV) and right atrium (RA), leftventricle (LV) and left atrium (LA), RV and LA, LV and RA, RV and LV andRA and LA. Furthermore, epicardiac and intra-thoracic electrodes couldalso be employed, e.g. using the IMD body or can 200 as one electrode.

Bipolar, tripolar or quadopolar measurements are possible and within thescope of the invention. Generally, better result is obtained if theelectrodes are not positioned too close.

As will be described in more detail herein, the monitoring system of theinvention or at least a portion therefore can be implemented in the IMD200. In an alternative approach, the monitoring system 100 or at least aportion therefore is implemented in an external device 300. Thisexternal device 300 could be a programmer as illustrated in the figure,a physician's workstation, a home monitoring device or actually any dataprocessing unit having capability of receiving data collected by the IMD200. The external device 300 could receive this data through directcommunication with the IMD 200 or via an intermediate communicationsmodule/unit operating as a relay device.

The external device 300 is preferably connected to a display screen 310allowing display of the calculated trend parameters of the invention forallowing the subject 1 or a physician to monitor the trend parameters.

FIG. 17 is a schematic block diagram of a monitoring system 100according to an embodiment of the invention. The system 100 comprises ageneral data input 110 for receiving impedance-related data collected bythe IMD. This input 110 could include a receiver chain of a wirelessreceiver, i.e. an antenna unit, demodulator and decoder. In such a case,the input data can be wirelessly transmitted from the IMD or anintermediate relay device to the system 100. In an alternative approach,the input 110 is adapted for receiving a data carrier, such as CD-disc,DVD-disc, USB-memory, etc. carrying the impedance related data. Alsoother inputs, e.g. network input, allowing a wired transmission of thedata to the monitoring system 100 are possible.

The monitoring system 100 further comprises a data processor 120arranged for generating a plurality of trend parameters. Each such trendparameter is obtained by collectively processing multiple cardiogenicimpedance values reflective of the impedance of the heart in connectionwith an inhalation-to-exhalation transition and multiple impedancevalues reflective of the impedance of the heart in connection with anexhalation-to-inhalation transition.

The generated trend parameters are forwarded from the data processor 120to a property monitor 130 of the system 100. This monitor 130 processesthe received trend parameter for allowing a monitoring of the mechanicalproperties of the subject's heart. In a preferred implementation, thisprocessing involves plotting the trend parameters versus recording timeon a connected display screen 310. This display screen could thendisplay any of the diagrams in FIG. 10, 11, 14 or 15 depending on theparticular parameter type that is generated by the data processor 120and the particular parameter processing conducted by the monitor 130.

A physician or even the patient himself/herself could view the screenand detect any change in the mechanical heart properties. This displayeddata can constitute decision support information for the physician fordetermining the likelihood of a deleterious heart condition, such asischemia, CHF, eminent hear attack, etc.

In a further implementation, the property monitor 130 instead or inaddition sounds an alarm if there is a large change in the processedtrend parameters. This could be an audio, tactile and/or visual alarmnotifying the particular subject. The monitor 130 also or insteadcompiles an alarm message that is displayed on the screen 310, sent by adata output (not illustrated) to a handheld device carried by thesubject, or sent by the data output to the subject's physician.

In an embodiment of the invention, the data received by the data input110 is the desired cardiogenic impedance data collected by the IMD. Inanother embodiment, the input data is “raw” voltage/current data orpartly processed such data. In such a case, the input data is forwardedfrom the input 110 to a calculator 160 arranged for calculating thedesired cardiogenic impedance values. The calculator 160 generates thefirst and second impedance value sets that are subsequently used by thedata processor 120 for generating the trend parameters.

In the case the input voltage/current data is not tagged for identifyingwhether the data is recorded in connection with a defined period of aheart cycle occurring in connection with an exhalation-to-inhalation orinhalation-to-exhalation transition in the respiratory cycle, the system100 comprises and uses a transition identifier 140. This identifier 140processes an input signal from the data input 110, such aspressure/sound recordings, IEGM recordings, respiratory impedancerecordings, collected in the subject. The identifier 140 monitors theinput signal for locating the time intervals corresponding to thetransitions. As the input signal is preferably collected by the IMD, thesignal can be time-marked with a same time reference as thevoltage/current data. This allows the identifier 140 to correctlyidentify the correct voltage/current samples to be used by thecalculator 160 when determining the cardiogenic impedance values.

In a preferred implementation, the system 150 comprises a calculator 150for calculating the respiratory impedance from input voltage/currentdata. This calculator 150 and the cardiogenic impedance calculator 160can be collectively implemented but equipped with different filters fordiscriminating between the impedance contribution from the respiratorysystem and from the cardiac system. In such a case, the calculatedrespiratory impedance signal is forwarded from the calculator 150 to thetransition identifier 140. The identifier searches for peaks and valleysin the impedance signal, which correspond to the desired respiratorytransitions.

The monitoring system 100 preferably also comprises a data storage 170for, at least temporary, storing data received by the input 110 andprocessed by the different units 120 to 160 of the monitoring system100. For example, calculated trend parameters from the data processor120 can be entered in the data storage 170 and stored therein until alater review occasion. In such a case, the parameters are fetched fromthe storage 170 and brought to the property monitor 130 for display onthe connected screen 310.

The units 110 to 160 of the monitoring system 100 may be provided ashardware, software or a combination of hardware and software. Themonitoring system 100, or a least a portion of its included units 110 to170, may be implemented in an IMD or an external device, preferablyhaving capability of communicating with an IMD.

FIG. 18 is a schematic block diagram of an embodiment of the dataprocessor 12 of FIG. 17. The data processor 120 comprises a data plotter122 arranged for plotting the cardiogenic impedance values of the secondvalue set as a function of the cardiogenic impedance values of the firstset to form multiple plot points. These plot points are processed by aparameter generator 124 for generating a trend parameter. This generator124 could for example be implemented for fitting an ellipse or astraight line to the multiple plot points. The generated trend parameteris then a parameter representative of the ellipse, such as major axis,angle, or the line, such as slope, correlation, MSE, as previouslydescribed.

The units 122 and 124 of the data processor 120 may be provided ashardware, software or a combination of hardware and software. The units122 and 124 may all be implemented in the data processor 120.Alternatively, a distributed implementation with at least one of theunits implemented in the monitoring system is also possible.

FIG. 19 is a schematic block diagram of an IMD 200 according to anembodiment of the present invention. The IMD 200 comprises a pulsegenerator and data sampler 280 having connected electrodes 212, 214,216. This generator 280 is arranged for applying a current or voltagesignal, preferably in the form of a train of current or voltage pulses,over two of the electrodes 212, 214. The resulting voltage or currentsignal is measured over two electrodes 214, 216 by a voltage or currentmeasuring functionality of the generator/sampler 280. In the figure, thegenerator/sampler 280 is connected to two leads 210 equipped with thecurrent/voltage electrodes 212, 214, 216. The number of used leads 210(one or more) and electrodes 212, 214, 216 (two, three or four), thepositioning of the electrodes 212, 214, 216 (RV, LV, RA, LA, epicardiac,intra-thoracic) and the types of electrodes 212, 214, 216 (tip, coil,ring) can be selected as previously described.

Information of the applied signal and the measured resulting signal isforwarded to an impedance calculator 260 of the IMD 200. This calculator260 determines the first set of multiple cardiogenic impedance valuesand the second set of multiple cardiogenic impedance values per measuredand monitored respiratory cycle. The two value sets are forwarded to adata processor 220 arranged for generating decision support informationuseful in monitoring the mechanical properties of the heart of thesubject, in which the IMD 200 is implanted. This generation is performedby collectively processing the cardiogenic impedance values of the firstand second set from the calculator 260. In a first embodiment, theprocessing involves tagging impedance values reflective of the impedanceof the heart in connection with the previously described transitions inthe respiratory cycle. In such a case, further data processing isrequired before the data can be used in the property monitoring of theinvention. In a second embodiment, the processing involves generating atrend parameter that is reflective of the difference in cardiogenicimpedance signal in the two transitions. This trend parameter is thenused as decision support information, preferably accompanied withfurther such parameters recorded at other time intervals.

The generated decision support information can be forwarded to a datastorage 270 for storage until a later retrieval. Upon data retrieval,the decision support information (trend parameter or tagged impedancedata) is forwarded to an input and output (I/O) unit 290(transmitter/receiver chain). This I/O unit 290 includes functionalitiesfor processing incoming and outgoing data messages, optionally includingmodulator/demodulator and coder/decoder functionality. The I/O unit 290is further preferably connected to an antenna arrangement 292 used fortransmitting and receiving radio packets to and from the external unit,respectively. However, the I/O unit 290 could also or alternatively useother forms of wireless techniques than radio frequency transmissionswhen communicating with the external device. The I/O unit 290 could forexample use an inductive antenna 294 for external wirelesscommunication.

The I/O unit 290 compiles a message and transmits the decision supportinformation to an external communications unit, such a programmer orphysician's workstation, preferably to a monitoring system of theinvention implemented in this external unit.

In an alternative approach, the information forwarded from thegenerator/sampler 280 to the calculator 260 is directly forwarded to theI/O unit 290 for transmission to the external unit. In such a case, themonitoring system implemented in that unit includes an impedancecalculator (see FIG. 17). Correspondingly, the impedance valuescalculated by the calculator 260 could be directly sent to the externalunit via the I/O unit 290. The data processing functionality will thenbe conducted in the monitoring system of that unit.

The units 220, 260, 280 and 290 of the IMD 200 can be provided ashardware, software or a combination of hardware and software.

FIG. 20 is a schematic block diagram illustrating a possibleimplementation of the impedance calculator 260 of FIG. 19. Thisimplementation could also be useful for the impedance calculator 160 ofFIG. 17. In this calculator embodiment, a current signal (I) is appliedover two electrodes and a resulting voltage signal (V) is measured. Themeasured AC voltage is optionally pre-amplified in an amplifier 261. Theamplified voltage signal is forwarded to an integrator 262 basicallyarranged for calculating the voltage area of the signal per pulse. Theintegrator 262 also integrates the applied current signal forcalculating the current area of the signal per pulse. The integratedabsolute impedance can then be calculated in block 263 as the quotientbetween the voltage area and the current area. This raw impedance signalis input into two parallel filter chains. The first chain involves abandpass filter 264 followed by a low-pass filter 265. The output fromthis filter chain is input to an analog to dialog (A/D) converter 268 toform the respiratory impedance signal Z_(r). The second chain comprisesa high-pass filter 266 followed by a low-pass filter 267. The filteroutput is processed through the A/D converted 268 to form thecardiogenic impedance signal Z_(c). Thus, a same input “raw” signal canbe used to obtain both the cardiogenic impedance signal, employed by theinvention, and the respiratory impedance signal, useful for identifyingcorrect portions in the cardiogenic signal, by different forms offiltering.

FIG. 21 is a schematic block diagram of another embodiment of an IMD 200according to the invention. This IMD 200 comprises the monitoring system100 of the invention used for generating a plurality of trendparameters. The operation of the units 220, 270, 280 and 290 is similarto what has previously described in connection with FIG. 19.Correspondingly, the operation of the transition identifier 240 issimilar to what has been described in connection with FIG. 17. Theproperty monitor 230 of the monitoring system 100 processes the trendparameters calculated by the data processor 220. The monitor 230 couldfor example time-stamp the different trend parameters or calculateaverage values from different sets of trend parameters. In a furtherembodiment, the property monitor 230 could monitor the different trendparameters to detect any sudden change in parameter values. In such acase, the monitor 230 can generate an alarm message to be sent to anexternal device by the I/O unit 290.

The units 220, 230, 260, 280 and 290 of the IMD 200 can be provided ashardware, software or a combination of hardware and software.

Although modifications and changes may be suggested by those skilled inthe art, it is the intention of the inventor to embody within the patentwarranted heron all changes and modifications as reasonably and properlycome within the scope of his or her contribution to the art.

I claim as my invention:
 1. A method of monitoring mechanical propertiesof a heart in a subject, comprising the steps of: a) determining a firstset of multiple cardiogenic impedance values reflective of the impedanceof said heart during a defined period of a heart cycle occurring inconnection with a transition from inhalation to exhalation in saidsubject; b) determining a second set of multiple cardiogenic impedancevalues reflective of the impedance of said heart during said definedperiod of a heart cycle occurring in connection with a transition fromexhalation to inhalation in said subject; c) collectively processingwith a data processor said multiple cardiogenic impedance values of saidfirst set as a function of said second set to determine a relationshipbetween the first and second set and analyzing the relationship betweenthe first and second sets to form a trend parameter representative ofrespiratory effect on said cardiogenic impedance values; d) repeatingsaid determining steps a), b) and processing step c) to form a pluralityof trend parameters over time; and e) monitoring said mechanicalproperties of said heart by processing said plurality of trendparameters.
 2. The method according to claim 1, wherein step a)comprises: applying a first current signal or a first voltage signal toat least a portion of said heart during a first portion of a respiratorycycle; measuring a first resulting voltage signal or a first resultingcurrent signal over at least a portion of said heart during said firstportion of said respiratory cycle; and generating said first set ofmultiple cardiogenic impedance values based on said first current signaland said first resulting voltage signal or said first voltage signal andsaid first resulting current signal; and wherein step b) comprises:applying a second current signal or a second voltage signal to at leasta portion of said heart during a second portion of said respiratorycycle; measuring a second resulting voltage signal or a second resultingcurrent signal over at least a portion of said heart during said secondportion of said respiratory cycle; and generating said second set ofmultiple cardiogenic impedance values based on said second currentsignal and said second resulting voltage signal or said second voltagesignal and said second resulting current signal.
 3. The method accordingto claim 1, wherein step c) comprises the steps of: plotting saidmultiple cardiogenic impedance values of said second set as a functionof said multiple cardiogenic impedance values of said first set toobtain multiple plot points; and generating said trend parameter byprocessing said multiple plot points.
 4. The method according to claim3, wherein said generating step comprises the steps of: fitting anellipse to said multiple plot points; and generating said trendparameter as a parameter being representative of said ellipse.
 5. Themethod according to claim 3, wherein said generating step comprises thesteps of: fitting a straight line to said multiple plot points;generating said trend parameter as a parameter being representative ofsaid straight line.
 6. The method according to claim 1, wherein step e)comprises plotting said plurality of trend parameters to display anychanges of said mechanical properties of said heart.
 7. The methodaccording to claim 6, wherein said changes of said mechanical propertiesare due to an ischemic heart disease, progression of heart failure orpoor inter-chamber synchronization of said heart.
 8. A method ofmonitoring mechanical properties of a heart in a subject, comprising thesteps of: a) determining a first set of multiple cardiogenic impedancevalues reflective of the impedance of said heart in connection with atransition from inhalation to exhalation in said subject; b) determininga second set of multiple cardiogenic impedance values reflective of theimpedance of said heart in connection with a transition from exhalationto inhalation in said subject: c) collectively processing with a dataprocessor said multiple cardiogenic impedance values of said first setas a function of said second set to determine a relationship between thefirst and second set and analyzing the relationship between the firstand second sets to form a trend parameter representative of respiratoryeffect on said cardiogenic impedance values; d) repeating saiddetermining steps a), b) and processing step c) to form a plurality oftrend parameters over time; e) monitoring said mechanical properties ofsaid heart by processing said plurality of trend parameters; f)identifying a first heart cycle occurring in connection with saidtransition from inhalation to exhalation; and g) identifying a secondheart cycle occurring in connection with said transition from exhalationto inhalation; and wherein step a) comprises determining multiplecardiogenic impedance values reflective of the impedance of said heartduring at least a portion said first heart cycle, and wherein step b)comprises determining multiple cardiogenic impedance values reflectiveof the impedance of said heart during at least a portion of said secondheart cycle.
 9. The method according to claim 8, further comprising thestep of: h) generating a signal of multiple respiratory impedance valuesof said subject; and wherein step f) comprises identifying said firstheart cycle as a heart cycle occurring in connection with a maximumvalue of said respiratory impedance signal during a respiration cycle,and wherein step g) comprises identifying said second heart cycle as aheart cycle occurring in connection with a minimum value of saidrespiratory impedance signal during said respiration cycle.
 10. Themethod according to claim 9, wherein step f) comprises identifying saidfirst heart cycle as a heart cycle coinciding with or being closest intime to said maximum value of said respiratory impedance signal duringsaid respiration cycle and wherein step g) comprises identifying saidsecond heart cycle as a heart cycle coinciding with or being closest intime to said minimum value of said respiratory impedance signal duringsaid respiration cycle.
 11. A system for monitoring mechanicalproperties of a heart in a subject, said system comprising: a dataprocessor that generates a plurality of trend parameters representativeof respiratory effect on cardiogenic impedance values by, for each trendparameter, collectively processing multiple cardiogenic impedance valuesreflective of the impedance of said heart during a defined period of aheart cycle occurring in connection with a transition from inhalation toexhalation in said subject as a function of multiple cardiogenicimpedance values reflective of the impedance of said heart during saiddefined period of a heart cycle occurring in connection with atransition from exhalation to inhalation in said subject to determine arelationship between the first and second set and analyzing therelationship between the first and second sets to form the trendparameters; and a property monitor that monitors said mechanicalproperties of said heart by processing said plurality of trendparameters.
 12. The system according to claim 11, wherein the dataprocessor is adapted to generate a plurality of first sets, each firstset comprising multiple cardiogenic impedance values reflective of theimpedance of said heart in connection with said transition frominhalation to exhalation in said subject, the data processor beingfurther adapted to determine a plurality of second sets, each second setcomprising multiple cardiogenic impedance values reflective of theimpedance of said heart in connection with said transition fromexhalation to inhalation of said subject.
 13. The system according toclaim 12, further comprising: a current applier that applies a currentsignal or a voltage signal to at least a portion of said heart; and avoltage measurer that measures a resulting voltage signal or a resultingcurrent signal over at least a portion of said heart, and wherein saiddata processor generates multiple cardiogenic impedance values based onsaid current signal and said resulting voltage signal or said voltagesignal and said resulting current signal.
 14. The system according toclaim 11, wherein said data processor comprises: a data plotter thatplots said multiple cardiogenic impedance values reflective of theimpedance of said heart in connection with said transition fromexhalation to inhalation as a function of said multiple impedance valuesreflective of the cardiogenic impedance of said heart in connection withsaid transition from inhalation to exhalation to obtain multiple plotpoints; and a parameter generator that generates a trend parameter byprocessing said multiple plot points.
 15. The system according to claim14, wherein said parameter generator i) fits an ellipse to said multipleplot points and ii) generates said trend parameter as a parameter beingrepresentative of said ellipse.
 16. The system according to claim 14,wherein said parameter generator fits a straight line to said multipleplot points and ii) generates said trend parameter as a parameter beingrepresentative of said straight line.
 17. The system according to claim11, wherein said property monitor plots said plurality of trendparameters on a connected display screen to display any changes of saidmechanical properties of said heart.
 18. A system for monitoringmechanical properties of a heart in a subject, said system comprising: adata processor that generates a plurality of trend parametersrepresentative of respiratory effect on cardiogenic impedance values by,for each trend parameter, collectively processing multiple cardiogenicimpedance values reflective of the impedance of said heart in connectionwith a transition from inhalation to exhalation in said subject as afunction of multiple cardiogenic impedance values reflective of theimpedance of said heart in connection with a transition from exhalationto inhalation in said subject to determine a relationship between thefirst and second set and analyzing the relationship between the firstand second sets to form the trend parameters; a property monitor thatmonitors said mechanical properties of said heart by processing saidplurality of trend parameters; an identification unit that i)identifies, for each first set, a first heart cycle of a respiratorycycle occurring in connection with said transition from inhalation toexhalation and ii) identifies, for each second set, a second heart cycleof said respiratory cycle occurring in connection with said transitionfrom exhalation to inhalation.
 19. The system according to claim 18,wherein said data processor i) determines, for each first set, multiplecardiogenic impedance values reflective of the impedance of said heartduring at least a portion of said first heart cycle, and ii) determines,for each second set, said multiple cardiogenic impedance valuesreflective of the impedance of said heart during at least a portion ofsaid second heart cycle.
 20. The system according to claim 19, furthercomprising a signal generator adapted to generate a signal of multiplerespiratory impedance values of said subject, and an identification unitadapted to identify for each first set, said first heart cycle as aheart cycle occurring in connection with a maximum value of saidrespiratory impedance signal during a respiration cycle, and for eachsecond set, said second heart cycle as a heart cycle occurring inconnection with a minimum value of said respiratory impedance signalduring said respiration cycle.
 21. The system according to claim 20,wherein said identification unit i) identifies, for each first set, saidfirst heart cycle as a heart cycle coinciding with or being closest intime to said maximum value of said respiratory impedance signal duringsaid respiration cycle and ii) identifies, for each second set, secondheart cycle as a heart cycle coinciding with or being closest in time tosaid minimum value of said respiratory impedance signal during saidrespiration cycle.
 22. An implantable medical device comprising: asystem that i) determines a first set of multiple cardiogenic impedancevalues reflective of the impedance of a heart during a defined period ofa heart cycle occurring in a subject in connection with a transitionfrom inhalation to exhalation in said subject, and ii) determines asecond set of multiple cardiogenic impedance values reflective of theimpedance of said heart during said defined period of a heart cycleoccurring in connection with a transition from exhalation to inhalationof said subject; and a data processor that generates decision supportinformation useful in monitoring mechanical properties of said heart bycollectively processing said first set of multiple cardiogenic impedancevalues as a function of said second set of multiple cardiogenicimpedance values to determine a relationship between the first andsecond set and analyzing the relationship between the first and secondsets to form the trend parameters.